Access Type

Open Access Dissertation

Date of Award

January 2013

Degree Type

Dissertation

Degree Name

Ph.D.

Department

Biomedical Engineering

First Advisor

Ewart M. Haacke

Abstract

The importance of iron in maintaining normal physiological processes in the human body has been well emphasized in the literature. However, "when iron behaves badly", its abnormal presence might lead to a spectrum of pathologies depending on what function has been altered. In the brain, for instance, abnormal iron content is thought to be associated with neurodegenerative diseases. In this dissertation, we study iron involvement in one of the most debilitating neurological diseases, multiple sclerosis (MS), using in vivo magnetic resonance imaging. We first test the sensitivity and specificity of the MR method used, known as susceptibility weighted imaging (SWI) compared to other conventional MR techniques and rapid-scanning X-ray fluorescence in MS cadaver brains. Then, we use SWI phase images to assess iron content in the deep gray matter structures of MS patients compared to normal controls. Finally, we assess the possibility of developing a new MS vascular animal model to study the link between vascular abnormalities, iron deposition and sclerotic lesions.

As a result of this work, we show that SWI provides a better contrast to image the structures and substructures of the brain based on their iron content compared to conventional MR techniques. The power of SWI in imaging iron content was validated by the use of X-Ray fluorescence (which is known to be an element specific imaging method), showing similar contrast and making SWI the method of choice to image iron content in vivo. Using SWI, we show a clear separation between MS patients and normal subjects, when we assessed iron content in the midbrain, thalamus and basal ganglia. We report that out of the seven structures studied, two were more susceptible to abnormal iron deposition (the pulvinar thalamus in young adults, and the red nucleus in elderly people). Finally, in an MR based study, we show that the swine and the human share a similar cerebrovascular drainage system starting from the superficial cerebral veins and deep cervical veins all the way to the heart, as a means to test the vascular involvement in MS.

Download

Share

COinS